The nuclear factor erythroid-derived 2-related factor 2 (NRF2) plays a pivotal role in the regulation of genes involved in oxidative stress and drug detoxification. Therefore, it is important to find NRF2 inducers to protect cells from excessive oxidative damage. Here, we investigated the effect of medicarpin isolated from the root of Robinia pseudoacacia L. on the activity of NRF2 in HeLa cells. Medicarpin significantly induced the antioxidant response elements (ARE)-luciferase activity in a concentration-dependent manner. Furthermore, medicarpin not only induced HO-1, GCLC, and NQO1 mRNA by translocating NRF2 to the nucleus but also induced the mRNA level of NRF2. To verify the NRF2 induction mechanism by medicarpin, ~2 kb of NRF2 promoter-luciferase assay was executed. As a result, medicarpin significantly induced NRF2-luciferase activity. Moreover, medicarpin strongly inhibited the ubiquitin-dependent proteasomal degradation of NRF2. Thus, medicarpin might protect cells by promoting the NRF2 transcriptional activity.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal-tract inflammation with dysregulated immune responses, which are partly attributable to dysbiosis. Given that diet plays a critical role in IBD pathogenesis and progression, we elucidated the effects of a high-fat diet (HFD) feeding on IBD development in relation to immune dysfunction and the gut microbiota. Five-week-old male C57BL/6J mice were fed either a normal diet (ND) or HFD for 14 weeks. The animals were further divided into ND, ND+ dextran sulfate sodium (DSS), HFD, and HFD+DSS treatment groups. The HFD+DSS mice exhibited lower body weight loss, lower disease activity index, longer colon length, and increased tight-junction protein expression and goblet-cell proportions compared with the ND+DSS mice. The T helper (h)1 and Th17 cell populations and pro-inflammatory cytokines involved in colitis pathogenesis were significantly more reduced in the HFD+DSS mice than in the ND+DSS mice. The HFD+DSS mice showed significantly increased serum leptin concentrations, colonic leptin receptor expression, enhanced anti-apoptotic AKT expression, and reduced pro-apoptotic MAPK and Bax expression compared with the ND+DSS mice, suggesting the involvement of the leptin-mediated pathway in intestinal epithelial cell apoptosis. The alterations in the gut-microbiota composition in the HFD+DSS group were the opposite of those in the ND+DSS group and rather similar to those of the ND group, indicating that the protective effects of HFD feeding against DSS-induced colitis are associated with changes in gut-microbiota composition. Overall, HFD feeding ameliorates DSS-induced colitis and colonic mucosal damage by reinforcing colonic barrier function and regulating immune responses in association with changes in gut-microbiota composition.

Camellia japonica L. (Theaceae) has been used for medicinal and cosmetic purposes in East Asian countries. Most functional components were obtained from the upper parts of the tree, such as leaves, flowers, or seeds. Here, we report a functional effect of the 80% methanolic extract of C. japonica root (CJRE) on antioxidative stress in HeLa cells. The nuclear factor erythroid-derived 2-related factor 2 (NRF2) is a key transcription factor that triggers the induction of oxidative stress-relating genes and drug detoxification. As result, CJRE showed a strong anti-radical scavenging effect in a dose-dependent manner. In addition, the induction of antioxidant response elements (ARE)-luciferase activity was maximized at CJRE 200 µg/mL. Furthermore, CJRE induced the mRNA levels of HO-1 and NQO1 by the nuclear NRF2 accumulation. As a possible mechanism of Nrf2 activation, the phosphorylation of p38 and ERK1/2 signaling might fortify the NRF2 induction as well as its stability. However, the phosphorylation of AKT is rather decreased. Taken together, CJRE may potentiate the antioxidant effects by increasing the NRF2 signaling through MAP kinase signaling and the properties of its radical scavenging activity. Thus, CJRE could apply for other medicinal and cosmetic purposes.

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